ISSN: 2469-5742 Kırlı et al. Int Arch Urol Complic 2019, 5:052 DOI: 10.23937/2469-5742/1510052 Volume 5 | Issue 1 International Archives of Open Access Urology and Complications

Research Article Endoscopic Vesicoureteral Reflux Treatment Outcomes in Patients with Voiding Dysfunction Elif Altınay Kırlı, Çağatay Doğan, Mehmet Hamza Gültekin, Zübeyr Talat and Bülent Önal*

Istanbul University–Cerrahpaşa Cerrahpaşa School of Medicine, Departmant of Urology, Turkey

*Corresponding author: Bülent Önal, MD, Professor, Department of Urology, Cerrahpaşa Faculty of Check for Medicine, Istanbul University, Turkey, Tel: +90-543-7955564; +90-212-4143000/21200 updates

Abstract Introduction Objective: Voiding dysfunction (VD) increases the Vesicoureteral reflux (VUR) is the most frequent frequency of vesicoureteral reflux (VUR). Subureteric urinary system anomaly of the pediatric population injection is an effective method for the treatment; however, with 1% incidence [1,2]. The main etiological cause is the presence of VD may affect the success rates. This study evaluated the results of single-session endoscopic the anatomically inadequate anti-reflux mechanism. treatment in patients admitting with VD symptoms who were Non-neuropathic lower urinary tract dysfunction diagnosed with VUR, and the effect of compliance to VD treatment on these results. (LUTD) is based purely on the fact that any neurologic lesions that can affect the lower urinary system can Materials and method: The data regarding patients who be identified [3]. In patients who also have voiding were being followed up for non-neurogenic VD diagnosis and who underwent subureteric injection or treated dysfunction (VD), especially who have impaired bladder conservatively was reviewed retrospectively in terms of compliance; VUR may develop due to impaired bladder follow up information and surgical outcomes. Endoscopic dynamic [4-6]. treatment was performed by applying dextranomer/ hyaluronic acid copolymer via submucosal route. Filling-phase and voiding phase dysfunctions are the Symptomatic and radiological assessments of the patients two main groups of LUTD. Detrusor can be over active on month 3 were reviewed. (DOA) as in over active bladder (OAB) or underactive Results: The data of 45 patients (67 renal unites (RU)) as in underactive bladder. Detrusor underactivity were assessed. 24 of them treated conservatively 21 of (DUA) denotes voiding contraction of reduced strength them underwent endoscopic subureteric injection (STING). resulting prolonged bladder emptying or failure to STING was performed for Grade 1 VUR in 3 RU, grade 2 in 12 RU, grade 3 in 16 RU, grade 4 in 2 RU, and grade 5 in 2 achieve complete emptying. Habitual postponing the RU. The success rate after subureteric injection treatment micturition is also in this group. Detrusor-sphincter was found to be 68%. VD treatment incompliance rate was interference is the main problem of voiding phase. This detected to be 31%, and infection rate during follow-up after condition can be a transitional phases of a complex injection to be 24%. sequence due to fact that should not be viewed as Conclusion: Providing regular treatment for voiding distinct entities [3,7,8]. dysfunction for at least 6 months before the endoscopic injection treatment for VUR accompanied by VD is The common problem in patients with VUR and important for increasing the success rates. That being said, VD is the renal injury developed as a result of urinary the success rate in this group might be lower than expected tract infections (UTIs) [9]. The coexistence of two pa- despite proper treatment for bladder. thologies may cause increase in the risk of renal failure. Keywords Therefore, VD investigation is an important part of the Vesicoureteral reflux, Voiding dysfunction, Subureteric diagnosis process in children diagnosed with VUR. injection

Citation: Kırlı EA, Doğan C, Gültekin MH, Talat Z, Önal B (2019) Endoscopic Vesicoureteral Re- flux Treatment Outcomes in Patients with Voiding Dysfunction. Int Arch Urol Complic 5:052.doi. org/10.23937/2469-5742/1510052 Accepted: January 26, 2019: Published: January 28, 2019 Copyright: © 2019 Kırlı EA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Kırlı et al. Int Arch Urol Complic 2019, 5:052 • Page 1 of 5 • DOI: 10.23937/2469-5742/1510052 ISSN: 2469-5742

Spontaneous resolution may occur in low-grade urinary tract, abdominal and pelvic muscles), habitual VUR especially detected in early childhood. That being regulations as fluid intake, regular voiding and dietary said, in cases in which urinary tract infection cannot be regulation for preventing constipation. Optimal void- controlled and scarring occurs, the preferred treatment ing position was demonstrated with the child in front is surgery irrespective of VUR grade [1]. Endoscopic of a mirror. Micturition was supervised and corrections subureteric injection (STING) in VUR treatment isa made until achieving patient’s cooperation [8]. minimally invasive and well-tolerated method, which In addition to standard urotherapy, antibiotherapy provides a cure rate similar to open surgery. Today, was initiated at suppressive dose in patients with UTI it is preferred as primary surgical approach for VUR that was proved by urinary culture (trimethoprim (1-2 [10-12]. Also, endoscopic approach in the patients mg/kg)- Sulfamethoxazole (10-15 mg/kg) or nitrofuran- with neuropathic bladder who may also have many toin (1 mg/kg) according to urinary culture features), comorbidities has been described as a preferable and laxative treatment was initiated for patients with method compared to open surgical approaches [10-13]. the complaint of constipation. The continuity of anti- This study mainly evaluated the efficacy of single- muscarinic treatment, antibiotic suppression and stan- session STING in a patient group detected to have dard urotherapy for 6 months was accepted as compli- coexisting VD and VUR, and the effect of compliance ance to medical treatment. to VD treatment on success rates. Also provides information about the follow-up of patients followed by Dimercaptosuccinic acid static scintigraphy (DMSA) conservatively. scanning was performed as a initial scan for renal function and scarring. Additionally, in the case of Materials and Method recurrent UTI or pyelonephritis under the antibiotic Medical records of 150 patients (216 renal unit suppression is the other indication of DMSA scans for (RU)) who diagnosed as VUR in the past 10 years were evaluating new scar formation. evaluated retrospectively. Patients who were treated STING was performed in all RU that require surgical due to VUR accompanied by VD and evaluated with management. STING indication for low-grade reflux DMSA and voiding cystourethrography examination at is UTI persisting under suppressive therapy and the the time of diagnosis and at least one VCUG examination detection of scarring in dimercaptosuccinic acid static during follow-up or post-operative period were accepted scintigraphy (DMSA) in renal unit (RU) at the timeof to study. 67 RU of a total of 45 patients with complete diagnosis. medical records, were assessed retrospectively for affect of medical treatment and urotherapy compliance Single-session subureteric injection treatment is per- on clinical findings and follow up period characteristics. formed by applying classic STING technique, which was described by O’Donnell and Puri. Zero lens cystoscope VUR grades were assessed radiologically by was used to identify ureterovesical junction (UVJ) and performing voiding cystourethrography before and 5Fr needle was inserted at 6 o’clock position. After en- after treatment [14]. All patients were assessed for tering the mucosa 2-3 mm distal to UVJ, needle was ad- VD before the endoscopic intervention using voiding vanced to submucosal plane for a distance of 4-5 mm. diary and if clinically indicated, urodynamics. Voiding An average of 0.5 cc of Dextranomer/hyaluronic acid dysfunction symptom score was used for quantitative copolymer injection was performed until the mound systematic review of the voiding symptoms and also becomes apparent [16]. used for follow-up [15]. Follow-up for the patients after the procedure was DUA diagnoses were made using urodynamics, and performed with routine outpatient clinic visits, and OAB diagnosis based on symptoms and urodynamics radiologically, using USG at month 1, and USG and findings. Oxybutynin (0.1-0.3 mg/kg, 3 times daily) VCUG at month 6. Complete regression or downgrading was initiated for antimuscarinic treatment in patients of reflux in VCUG was considered as success and diagnosed with DOA or OAB. persisting or increasing reflux grade during follow-up Post-void residual urine was evaluated according was considered as failure. Statistical evaluation was to age-based criteria of International Children’s Con- performed using Wilcoxon Signed Rank test. tinence Society and clean intermittent catheterization Results was recommended in DUA patients with post-void re- sidual urine [8]. Patients were assessed for constipation 67 RU belong to forty-five patients (34 females, 11 and urinary tract infection in their initial and follow-up males) were evaluated. Twenty-four patients (32 RU) visits. were treated conservatively and 21 patients (35 RU) had STING procedure. All patients were introduced for standard urothera- py. Educational session at the standard urotherapy con- First presenting complaints were detected to be UTI sist of informative session (for anatomy and function of (n = 23, 51%), incontinence (n = 15, 33%), previously

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Table 1: Demographic features of patients according to treatment approach. Treatment Approach (n, %) Conservative Surgical Intervention 24 (53) 21 (47) Age (year) 7.2 ± 3.6 7.9 ± 8.2 Gender Male 3 (12) 8 (38) Female 21 (88) 13 (62) Complaint UTI 15 (62) 8 (38) VUR 1 (4) 3 (14) Abdominal pain 0 (0) 3 (14) Incontinence 8 (34) 7 (34) Diagnose Over active bladder 23 (95) 18 (86) Detrusor underactivity 1 (5) 3 (14)

Table 2: Evaluation of RU according to treatment approach and compliance to urotherapy and medical treatment. Treatment Approach Treatment Response Conservative Treatment Surgical Intervention Compatible Incompatible Compatible Incompatible Resolution 18 (56) 3 (9) 15 (43) 1 (3) Downgrading 5 (16) 2 (7) 6 (17) 2 (5) Stable 1 (3) 3 (9) 3 (9) 8 (23) Total 24 (75) 8 (25) 24 (69) 11 (31) detected VUR (n = 4, 9%) and abdominal pain (n = 3, was 69%. Decrease of reflux grade in post treatment 7%). VCUG is statistically significant and success rate sis 60% in these patients (p = 0.001). The rate of success After the initial evaluation of the patients, the in patients who do not comply with treatment is 31%. presence of OAB (n = 41, 91%) symptoms and findings, There was no significant decrease in VUR grade (p= DUA (n = 4, 9%), and the coexistence of VUR were 0.063) after injection. Evaluation of RUs according detected. Demographic features of patients according to treatment approach and compliance to standard to treatment approach were summarized in Table 1. urotherapy and medical treatment were summarized in Grade 1 VUR in 8 (25%), grade 2 in 13 (41%), grade 3 Table 2. in 9 (28%) and grade 4 in 2 (6%) were detected in pre- During follow-up, it was detected that 11% (n = treatment VCUG examination of patients who managed 5, 9 RU) of the patients had recurrent urinary tract conservatively. VUR was detected in left in 13 (54%) infection with fever. All these patients were previously right in 3 (13%) and bilateral in 8 (33%) patients. Grade underwent STING due to recurrent UTI in conservative 1 VUR in 3 (9%), grade 2 in 12 (34%), grade 3 in 16 (45%) treatment. Pyuria detected in urine analysis and urine and grade 4 in 2 (6%) grade 5 in 2 (6%) were detected cultures were positive for bacteria. Two patients in pre-treatment VCUG examination of patients who diagnosed as pyelonephritis. Three (15%) of the managed surgically. VUR was detected in left in 7 (33%) patients with recurrent UTI had new scarring in DMSA. and bilateral in 14 (66%) patients. Nine RU belongs to these patients underwent open DMSA examination at the time of diagnosis inpa- surgical intervention due to repeating UTI episodes. tients who required surgical management (n = 32 RU) Although the grade of VUR in this RU decreased after showed function below 40% in 7 RU (22%) and scarring reimplantation surgery recurrent UTI was detected in a in 12 RU (38%). Renal scarring was detected in 4 bilat- patient (1 RU, 12%). Grade of VUR decrease in 4 (44%), eral VUR patients (3 patients affected bilateral). Patient resolve in 4 RU (44%) after reimplantation and UTI did treated conservatively have normal renal functions not occur in these patients under suppression. without any scar formation in DMSA examination. Other patients who underwent STING or following When the patients were evaluated according to the conservatively did not have documented UTI in follow-up. standard urotherapy and medical treatment compli- Nineteen of conservatively treated patients had ance, it was seen that the compliance of the patients constipation at the time of diagnosis. Constipation treated with conservative treatment was 75%. Decrease improved in 12 in compatible, 3 in incompatible patients. of reflux grade in post treatment VCUG is statistically Seven of surgically treated patients had constipation significant with a success rate of 72% (p = 0.001). The at the time of diagnosis. Constipation improved in 6 in rate of success in patients who do not comply with compatible, 1 in incompatible patient. treatment is 16%. There was no significant decrease in Urinary incontinence was detected as presenting VUR grade (p = 0.0039) during follow up. symptom in 15 patients and none of these patients has The compliance of the patients treated with STING VUR more then grade 3. Symptom completely resolves

Kırlı et al. Int Arch Urol Complic 2019, 5:052 • Page 3 of 5 • DOI: 10.23937/2469-5742/1510052 ISSN: 2469-5742 in 11 patients after standard urotherapy and medical spontaneous resolution was not detected as at high management. rates as expected was also a warning sign for VD. The positive correlation between constipation and VD was No injection material migration or an obstructive clearly reported in the literature [18]. We detected that complication was detected in patients who underwent this pathology which may cause VD in a low number endoscopic treatment or open surgery. of patients at admittance was questioned and treated Discussion at low rates. Therefore, we believe that in case a UTI which cannot be controlled using prophylaxis especially VUR resolution rate following single injection for in bilateral and low-grade VUR is detected, performing grade 1 and 2 was 78%, 72% for grade 3, 63% for grade a detailed assessment for VD and constipation would 4 and 51% for grade 5. The total success rate with affect the treatment period positively. In this study, one and multiple injection was 85%. The success rate proper medical (prophylactic antibiotic, antimuscarinic) was reported as 74% for normal, 62% for neuropathic and behavioral treatment (standard urotherapy) was bladder [17]. This study detected a success rate of initiated in all patients before endoscopic surgery. The 68% for endoscopic treatment in the patient group success rate was found to be high in the patients, which with coexisting VD and VUR. While this rate is lower complied with treatment. This can be explained by compared to the patients without VD who underwent the fact that the bladder treatment prepared a proper endoscopic treatment, it is consistent with the finding background for endoscopic surgery. Therefore, it should of low success rates after neurogenic or non-neurogenic be remembered that the success rates in patients with bladder interventions as reported in larger series VD may not be at the expected level. Urinary diversion [10,11,17]. could be a temporarily option till improving patient Läckgren, et al. have reported that repeating compliance and bladder condition. Surgical cure may endoscopic treatment in coexisting bladder dysfunction be preferred in patients who had or would have failure and VUR provides a success rate of 83% [14]. The fact with endoscopic treatment. that treatment outcomes of all of the study patients As for complications, in their study, Capozza, et al. were evaluated after single-session injection in our study have reported that most of the patients with implant is a negative factor on our success rate, and also, most of the study patients had grade 3 or higher reflux grade. migration and who were considered to have treatment The reason for not repeating STING is the occurrence failure are being followed-up for VD diagnosis [11]. In of frequent UTI episodes in patients who were decided our study, obstructive complications was not detected to undergo open surgery and the detection of new in patients who underwent endoscopic treatment or scarring during follow-up. One of the main goals in VUR open surgery. treatment is preventing UTI, which may lead to renal Conclusion failure [1,9]. In the same study, it has been stated that bladder dysfunction resolved in 59% of the patients and Management of VD reduces the requirement of urinary tract infection was not observed again in 83% of surgical intervention by reducing the rate of UTI and the patients [14]. While we do not think that endoscopic leads to downgrading or complete resolution of VUR. treatment has effects on bladder functions, we believe Treatment for VD before the endoscopic treatment that previously administered anticholinergic treatment may provide increase in success rates Therefore, in VUR has effect on this outcome. In this respect, the success treatment, patients should be informed for importance rate in study subjects is higher that the resolution rate of compliance to medical treatment for VD, and if of VUR. The findings of regression of VD complaints and endoscopic injection treatment is being planned, a the decreasing incidence of urinary tract infections are regular treatment must be provided for at least 6 months consistent with this study. before the procedure. It should be remembered that It is known that UTI and reflux grade decreases using success rates may be low despite proper VD treatment, proper bladder treatment in patients who are being and surgical approaches should be in the forefront if followed-up for VD. The preparation of proper bladder necessary. background for urinary tract surgeries to be performed Financial Disclosure is a factor which increasing the success rates [1,17]. In conservatively treated patient’s success rate is higher, The authors declared that this study received no who were compatible to urotherapy and regular use of financial support. medical treatment. When we evaluated the presenting Ethics Committee Approval complaints of the patients, we detected that symptoms suggesting VD such as incontinence are present in a low This study was approved by Istanbul University number of patients, and signs which develop as a result Ethical Committee. of combined UTI and VUR even at low grades are in All authors equally contributed to the manuscript. the forefront. Suppression of overactivity and UTI may lead to resolve of urinary incontinence. The fact that The authors have nothing to disclosure.

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